Recent advances in PLGA particulate systems for drug delivery

PLGA is a FDA-approved biocompatible and biodegradable polymer that is widely used in biomedical fields including drug delivery. Micro and nanoparticles based on PLGA have been extensively studied as drug delivery systems. Numerous studies proved that PLGA particulate systems are highly promising drug carriers for tumor targeting as well as pulmonary, oral, ophthalmic and vaginal delivery. PLGA particles can load a variety of classes of drugs including peptides, proteins and siRNA, protect unstable drugs in the body and have an ability to adapt versatile surface functionalities. PLGA particle systems have evolved with advancement of nano and biotechnology in the past decade. This review focuses on novel and innovative PLGA-based particulate drug delivery carriers in recent years.     

Recent advances in the discovery and delivery of vaccine adjuvants

Adjuvant design has historically had a touch of alchemy at its heart due to its reliance on the complex biology of innate immune activation. However, a new mechanistic understanding of innate immunity, combined with new adjuvant and delivery platforms for exploiting this knowledge, has led to significant advances recently. Although many challenges remain, the field is moving rapidly and the proper tools and methodologies are in place for the use of traditional drug discovery engines in guiding the development of vaccine adjuvants. In this review, we outline the current trends in immune potentiator, delivery system and adjuvant design that will shape the vaccines of the future.     

Plasmid delivery to muscle: Recent advances in polymer delivery systems

Preclinical studies involving intramuscular injection of plasmid into animals have revealed at least four significant variables that effect levels of gene expression (i.e., >fivefold effect over controls), including the formulation, injection technique, species and pretreatment of the muscle with myotoxic agents to induce muscle damage. The uptake of plasmid formulated in saline has been shown to be a saturable process, most likely via a receptor-mediated event involving the T tubules and caveolae. Pharmacokinetic studies have demonstrated that the bioavailability of injected plasmid to muscle cells is very low, due to rapid and extensive plasmid degradation by extracellular nucleases. We have developed protective, interactive, non-condensing (PINC) delivery systems designed to complex plasmids and to (i) protect plasmids from rapid nuclease degradation, (ii) disperse and retain intact plasmid in the muscle and (iii) facilitate the uptake of plasmid by muscle cells. PINC systems result in up to at least a one log increase in both the extent and levels of gene expression over plasmid formulated in saline. We have combined the PINC delivery systems with two different muscle-specific expression plasmids. After direct intramuscular injection of these gene medicines, we have shown both local myotrophic and neurotrophic effects of expressed human insulin-like growth factor (hIGF-I) and the secretion of biologically active human growth hormone (hGH) into the systemic circulation.     

Recent advances in intraocular drug delivery systems

Vitreoretinal diseases are refractory to both topical and systemic pharmacological approaches because of specific environment of the eye. That is, the cornea, the sclera, nasolacrimal drainage of tears, frontward stream of aqueous humor, blood-aqueous barrier, and blood-retinal barrier strictly limit penetration and diffusion of drug into the retina. However, recent advances in intraocular drug delivery systems (DDS) have enabled drug to be delivered effectively into the eye. Clinically successful or promising cases involve non-biodegradable implants and inserts, biodegradable inserts and microparticles, intravitreal or sub-Tenon's injection of triamcinolone acetonide, and a photodynamic therapy (PDT) with verteporfin, a photosensitizer. More recently, a variety of pharmacological challenges to treat exudative age-related macular degeneration and macular edema are proceeding into clinical trials, as soon as anti-vascular endothelial growth factor (anti-VEGF) therapies have been proved to be effective by repeated intravitreal injections. In the near future, DDS must be required not only to develop a new treatment modality but also to improve efficacy and/or reduce injection numbers of currently available drugs. Here we introduce controlled release of drug and discussion of recent patents with biodegradable or non-biodegradable implants and drug targeting by modification of systemically administered drug.     

Recent advances in brain tumor-targeted nano-drug delivery systems

Introduction: Brain tumors represent one of the most challenging and difficult areas in unmet medical needs. Fortunately, the past decade has seen momentous developments in brain tumor research in terms of brain tumor-targeted novel nano-drug delivery systems with significant important superiority over conventional formulations with respect to decreased toxicity and improved pharmacokinetics/pharmacodynamics.

Area covered: This review first introduces the characteristics of the two major obstacles in brain-tumor targeted delivery, blood–brain barrier (BBB) and blood–brain tumor barrier (BBTB), and then reviews recent advances in brain tumor-targeted novel nano-drug delivery systems according to their targeting strategies aimed at different stages of brain tumor development and growth.

Expert opinion: Based on continuously changing vascular characteristics of brain tumors at different development and growth stages, we propose the concept of ‘whole-process targeting’ for brain tumor for nano-drug delivery systems, referring to a series of overall targeted drug delivery strategies aimed at key points during the whole development of brain tumors.     

Recent advances in inorganic nanoparticle-based drug delivery systems

Drug delivery systems, designed to enhance drug efficacy and reduce their adverse effects, have evolved accompanied by the development of novel materials. Nanotechnology is an emerging scientific area that has created a variety of intriguing inorganic nanoparticles. In this review, we focus on the feasibility of inorganic nanoparticles, including iron oxide nanoparticles, gold nanoparticles, fullerenes and carbon nanohorns, as drug carriers, and summarize recent advances in this field.     

Recent advances in brain tumor-targeted nano-drug delivery systems

INTRODUCTION: Brain tumors represent one of the most challenging and difficult areas in unmet medical needs. Fortunately, the past decade has seen momentous developments in brain tumor research in terms of brain tumor-targeted novel nano-drug delivery systems with significant important superiority over conventional formulations with respect to decreased toxicity and improved pharmacokinetics/pharmacodynamics. AREA COVERED: This review first introduces the characteristics of the two major obstacles in brain-tumor targeted delivery, blood-brain barrier (BBB) and blood-brain tumor barrier (BBTB), and then reviews recent advances in brain tumor-targeted novel nano-drug delivery systems according to their targeting strategies aimed at different stages of brain tumor development and growth. EXPERT OPINION: Based on continuously changing vascular characteristics of brain tumors at different development and growth stages, we propose the concept of 'whole-process targeting' for brain tumor for nano-drug delivery systems, referring to a series of overall targeted drug delivery strategies aimed at key points during the whole development of brain tumors.     

树状大分子作为新型药物载体的研究进展

树状大分子是一类高度枝化的单分散性大分子，其内部结构呈疏水性，外表面呈亲水性，可称为“单分子胶束”。本文在简介树状大分子的发展及结构特点的基础上，阐述了树状大分子作为药物载体的作用特点及其与药物的结合方式。目前，树状大分子在介导药物靶向传递及基因转染等方面的应用也备受关注，是一种颇有发展潜力的新型载体。     

Recent advances in testing of microsphere drug delivery systems

ABSTRACT

Introduction: This review discusses advances in the field of microsphere testing.

Areas covered: In vitro release-testing methods such as sample and separate, dialysis membrane sacs and USP apparatus IV have been used for microspheres. Based on comparisons of these methods, USP apparatus IV is currently the method of choice. Accelerated in vitro release tests have been developed to shorten the testing time for quality control purposes. In vitro-in vivo correlations using real-time and accelerated release data have been developed, to minimize the need to conduct in vivo performance evaluation. Storage stability studies have been conducted to investigate the influence of various environmental factors on microsphere quality throughout the product shelf life. New tests such as the floating test and the in vitro wash-off test have been developed along with advancement in characterization techniques for other physico-chemical parameters such as particle size, drug content, and thermal properties.

Expert opinion: Although significant developments have been made in microsphere release testing, there is still a lack of guidance in this area. Microsphere storage stability studies should be extended to include microspheres containing large molecules. An agreement needs to be reached on the use of particle sizing techniques to avoid inconsistent data. An approach needs to be developed to determine total moisture content of microspheres.     

Recent advances in crystalline and amorphous particulate protein formulations for controlled delivery

The number of particulate delivery systems for biologics is negligible compared to liquid dosage forms, signifying the complications associated with development of solid protein delivery systems. Particulate protein delivery systems can improve stability, reduce viscosity of suspensions at high protein concentration and allow for controlled drug release. This review discusses current advances in controlled delivery of particulate protein formulations. While the focus lies on protein crystals and delivery systems employing protein crystals, amorphous protein particles will also be addressed. Crystallization and precipitations methods and modifications allowing controlled delivery with and without encapsulation are summarized and discussed.     

Recent advances in delivery systems for anti-HIV1 therapy

In the last years, different non-biological and biological carrier systems have been developed for anti-HIV1 therapy. Liposomes are excellent potential anti-HIV1 carriers that have been tested with drugs, antisense oligonucleotides, ribozymes and therapeutic genes. Nanoparticles and low-density lipoproteins (LDLs) are cell-specific transporters of drugs against macrophage-specific infections such as HIV1. Through a process of protein transduction, cell-permeable peptides of natural origin or designed artificially allow the delivery of drugs and genetic material inside the cell. Erythrocyte ghosts and bacterial ghosts are a promising delivery system for therapeutic peptides and HIV vaccines. Of interest are the advances made in the field of HIV gene therapy by the use of autologous haematopoietic stem cells and viral vectors for HIV vaccines. Although important milestones have been reached in the development of carrier systems for the treatment of HIV, especially in the field of gene therapy, further clinical trials are required so that the efficiency and safety of these new systems can be guaranteed in HIV patients.     

Recent advances in protein and peptide drug delivery systems

Delivery of therapeutic proteins/peptides has received a considerable amount of attention over the last 10 years, but there are number of limitations to oral delivery of proteins. The barriers to peptide bioavailability after oral administration are intestinal membrane permeability, size, intestinal and hepatic metabolism and lastly solubility. A number of approaches have been used to overcome these limitations. Poor membrane permeabilities of hydrophilic peptides might be overcome by structurally modifying the compound, thus increasing their membrane partition characteristics and their affinity for carrier proteins. Another approach is site specific delivery of the peptides to the most permeable part of the intestine. Metabolism (hepatic and intestinal) of peptides might be controlled by co-administration of competitive enzyme inhibitors, structural modifications and administration of the compound as well as absorbed prodrug that is converted into therapeutically active agent after its absorption. Various delivery systems like prolease technology, nano-particulate and microparticulate delivery system, mucoadhesive delivery of peptides and microspheres have been developed for the delivery of proteins and peptides. Non-conventional delivery systems for proteins are biodegradable and non-biodegradable systems. Besides these, some other approaches for protein and peptide delivery are vector mediated delivery of proteins using adenovirus, macroflux transdermal patches, pulmonary delivery of proteins, delivery of proteins and peptides across blood brain barrier.     

透血脑屏障制剂的研究进展

透血脑屏障的研究是药剂学研究中的一个热点和难点，目前研究较多的途径是静脉注射纳米粒和鼻腔给药。综述了纳米粒的载药方法和透血脑 屏障的机制，通过鼻腔给药实现透血脑屏障的途径，影响药物从嗅觉区进入中枢神经系统的因素以及大分子药物利用该途径的可能性。     

Mucosal immunisation: adjuvants and delivery systems

The mucosal administration of vaccines is an area currently receiving a high level of interest due to potential advantages offered by this technique. These advantages include the ability to administer vaccines without need for needles, thus improving patient compliance with vaccination schedules, and the capacity to induce immune responses capable of preventing infections at the site of acquisition. Despite these advantages a number of limitations exist which currently inhibit our ability to successfully develop new mucosal vaccines. As such, much research is currently focused on developing new adjuvants and delivery systems to overcome these difficulties. However, despite high levels of interest in this area, relatively few mucosal vaccine candidates have successfully progressed to human clinical trials. In the review that follows, we aim to provide the reader with an overview of the immune system with respect to induction of mucosal immune responses. Furthermore, the review provides an overview of a number of microbial (bacterial toxins, CpG DNA, cytokines/chemokines, live vectors, and virus like particles) and synthetic (microspheres, liposomes, and lipopeptides) strategies that have been investigated as adjuvants or delivery systems for mucosal vaccine development, with a focus on the delivery of vaccines via the oral route.     

脂质体递药系统的临床研究进展

本文将脂质体递药系统按结构、组成和功能分成普通脂质体、多囊脂质体、长循环脂质体、热敏脂质体和免疫脂质体5类，分别介绍其应用和临床研究进展。     

作用于新生儿Fc受体药物递送系统研究进展

新生儿Fc受体(FcRn)最早发现是母体抗体传递给胎儿和新生儿的膜表面蛋白,后来也证明在成人体内也在多器官、多组织中终生表达,其维持着免疫球蛋白G和血清白蛋白在机体中的长循环和动态平衡,在固有免疫和适应性免疫调节中发挥着极为重要的作用。在现代生物制药研究中, FcRn是良好的药物递送靶点,也是目前研究的热点。本文简述了FcRn的基本生物学性质和作用机制,以及目前常用的FcRn的药物载体设计策略,特别是对于延长半衰期、靶向输送、跨生物膜及抗原递呈等多方面的功能应用进行展望。FcRn在不同组织内的分布和生物学功能,为未来基于FcRn的新型药物递送系统研究和免疫治疗方面等提供更广阔的思路。     

Recent advances in the targeting of systemically administered non-viral gene delivery systems

ABSTRACT

Introduction: Systemically administered non-viral gene delivery systems face multiple biological barriers that decrease their efficiency. These systems are rapidly cleared from the circulation and sufficient concentrations do not accumulate in diseased tissues. A number of targeting strategies can be used to provide for sufficient accumulation in the desired tissues to achieve a therapeutic effect.

Areas covered: We discuss recent advances in the targeting of non-viral gene delivery systems to different tissues after systemic administration. We compare passive and active targeting applied for tumor delivery and propose some strategies that can be used to overcome the drawbacks of each case. We also discuss targeting the liver and lungs as two particularly important organs in gene therapy.

Expert opinion: There is currently no optimum non-viral gene delivery system for targeting genes to specific tissues. The dose delivered to tumor tissues using passive targeting is low and shows a high patient variation. Although active targeting can enhance binding to specific cells, only a few reports are available to support its value in vivo. The design of smart nanocarriers for promoting active targeting is urgently needed and targeting the endothelium is a promising strategy for gene delivery to tumors as well as other organs.